The serotonin hypothesis of obsessive compulsive disorder: implications of pharmacologic challenge studies.
ABSTRACT Demonstration of the efficacy of serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors such as clomipramine in the treatment of obsessive compulsive disorder has fueled interest in the neurobiological basis of this illness. Results of treatment studies, investigations of biological markers, and pharmacologic challenges are reviewed and implications for a 5-HT theory of obsessive compulsive disorder discussed. While the nature of the dysregulation in serotonin transmission that may attend obsessive compulsive disorder has yet to be fully elucidated, evidence accumulates that 5-HT function in part modulates obsessive compulsive symptoms. Development of more specific probes and new brain imaging techniques will further enhance understanding of the pathophysiology of obsessive compulsive disorder.
SourceAvailable from: Darin D Dougherty[Show abstract] [Hide abstract]
ABSTRACT: Obsessive-compulsive disorder (OCD) is a chronic, severe mental illness with up to 2-3% prevalence worldwide. In fact, OCD has been classified as one of the world's 10 leading causes of illness-related disability according to the World Health Organization, largely because of the chronic nature of disabling symptoms.() Despite the severity and high prevalence of this chronic and disabling disorder, there is still relatively limited understanding of its pathophysiology. However, this is now rapidly changing due to development of powerful technologies that can be used to dissect the neural circuits underlying pathologic behaviors. In this article, we describe recent technical advances that have allowed neuroscientists to start identifying the circuits underlying complex repetitive behaviors using animal model systems. In addition, we review current surgical and stimulation-based treatments for OCD that target circuit dysfunction. Finally, we discuss how findings from animal models may be applied in the clinical arena to help inform and refine targeted brain stimulation-based treatment approaches. © 2015 Wiley Periodicals, Inc.Depression and Anxiety 05/2015; DOI:10.1002/da.22367 · 4.29 Impact Factor
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ABSTRACT: Locations of cerebral perfusion abnormalities in obsessive-compulsive disorder (OCD) were mapped with single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). This report is a new, more thorough analysis of a previous study of these subjects that used region-of-interest methods. Ten obsessive-compulsive patients and seven age- and sex-matched control subjects were studied. Image sets were converted into stereotaxic space, normalized to each subject's mean cerebral value, then group averaged. Difference images were calculated and searched for regions with significant between-group cerebral perfusion differences. Obsessive-compulsive patients had significantly higher relative cerebral perfusion in medial-frontal and right frontal cortex and in cerebellum, and significantly reduced perfusion in right visual association cortex. Increased frontal Perfusion agrees with several prior reports. The caudate nucleus, which has been controversial in neuroimaging studies of OCD, did not display a difference between groups. The results of this study provide information about the locations and extents of cerebral perfusion abnormalities in OCD. Regional abnormalities were compared with those reported in prior functional neuroimaging studies. Issues related to OCD hyperfrontality and frontal lateralization of psychopathology are discussed. Normal caudate nucleus findings are considered in relation to prior functional imaging studies and hypotheses of OCD pathology. © 1994 Wiley-Liss, Inc.Human Brain Mapping 01/1994; 1(4):237-48. DOI:10.1002/hbm.460010403 · 6.92 Impact Factor
European Neuropsychopharmacology 09/1993; 3(3):229. DOI:10.1016/0924-977X(93)90042-K · 5.40 Impact Factor